The deuterated
benzaldehyde derivative
zilascorb(2H), 5,6-O-benzylidene-d-L-ascorbic
acid, was administered once daily by i.v. injection in nude mice with grafted tumours of a human
malignant melanoma (E.E.) and ovarian
carcinoma (OVCAR-3) origins. Like
benzaldehyde,
zilascorb(2H) has been shown to induce
protein synthesis inhibition at otherwise non-toxic doses in cells grown in vitro, and acts reversibly in the sense that
protein synthesis returns to normal shortly after removal of the
drug. The present data indicate that daily
injections with
zilascorb(2H) induce a tumour volume growth inhibitory effect in both tumour xenografts studied. Furthermore, from histological examinations of each single tumour it was found that tumours of
drug-treated animals, although smaller than those of placebo-treated (i.e. control) animals, had, on average, a higher necrotic fraction than control tumours. Thus, it is concluded that
zilascorb(2H) induces tumour necrotisation and not just inhibition of the rate of tumour cell production. Continued measurement of tumour volume after ended treatment with
zilascorb(2H) indicated that surviving tumour cells resumed their normal growth rate immediately. The reversibility of the effect induced by this compound, earlier observed in vitro only, is therefore here confirmed to be valid also in two different tumour xenografts in vivo. The present data accords well with the assumption that
protein synthesis inhibition is the primary cellular effect of
zilascorb(2H) in vivo. We therefore conclude that zilascorb(2H)-induced
cancer cell lethality in tumour xenografts probably comes as a secondary consequence of prolonged
protein synthesis inhibition.